Assessment of the utility of biomarkers of osteoarthritis in the guinea
Assessment of the utility of biomarkers of osteoarthritis in the guinea
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DOI：
10.1016/j.joca.2006.03.007
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发表时间：
2006-09-01
影响因子：
7
通讯作者：
Kraus, V. B.
中科院分区：
文献类型：
--
作者：
Huebner, J. L.;Kraus, V. B.
目的：为了确定豚鼠骨关节炎（OA）的生化标志物，我们的特点是四个生物标志物和17个细胞因子的年龄和应变相关的differentiation.Methods：两个豚鼠品系在这项研究中进行了检查：（1）哈特利（OA倾向）和（2）应变13（OA耐药）。在两种豚鼠品系中定量滑液硫酸角质素（KS）和软骨寡聚基质蛋白（COMP）水平以及血清C2C、CPII和一组细胞因子和趋化因子水平。其中包括：IL-1 α、IL-1 β、IL-2、IL-3、IL-4、IL-5、IL-6、IL-10、IL-12 p40、IL-12 p70、IL-17、G-CSF、GM-CSF、IFN-γ、KC、MIP-1 α、RANTES和TNF-α。早在2月龄时，与品系13动物相比，Hartley动物膝关节中这些生物标志物的滑液浓度升高。早在4月龄时，代表11型胶原降解和合成比率的血清C2C/CPII水平在OA易感的Hartley中与品系13动物相比升高。此外，在12个月大时，16种细胞因子和趋化因子中有11种存在明显的菌株相关差异。使用多元线性回归，血清IL-6和TNF-α浓度分别与品系、体重及其相互作用密切相关（IL-6的r（2）= 0.80，P = 0.0002; TNF-α的r（2）= 0.55，P = 0.02）。来自滑液的生物标志物反映了豚鼠自发性OA模型中的组织学严重程度。滑液生物标志物特征表明，早在2月龄时，Hartley品系的软骨基质周转就加速了，这是在组织学损伤证据之前。Hartley菌株还举例说明了II型胶原代谢的不平衡和指示促炎状态的血清细胞因子/趋化因子谱。这些发现阐明了豚鼠中与人类OA相关的其他疾病相关特征。(C)2006年国际骨关节炎研究学会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To identify biochemical markers of osteoarthritis (OA) in the guinea pig, we characterized four biomarkers and 17 cytokines for age- and strain-related differences.Methods: Two guinea pig strains were examined in this study: (1) the Hartley (OA-prone) and (2) Strain 13 (OA-resistant). Levels of synovial fluid keratan sulfate (KS) and cartilage oligomeric matrix protein (COMP), as well as levels of serum C2C, CPII, and a panel of cytokines and chemokines were quantified in both guinea pig strains. These included: IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-17, G-CSF, GM-CSF, IFN-gamma, KC, MIP-1 alpha, RANTES, and TNF-alpha.Results: Synovial fluid concentrations of KS and COMP increased coincident with histological OA and correlated positively with the severity of histological damage in both strains. Synovial fluid concentrations of these biomarkers were elevated in the knees of the Hartley compared to the Strain 13 animals, as early as 2 months of age. From as early as 4 months of age, the levels of serum C2C/CPII, representing the ratio of type 11 collagen degradation and synthesis, were elevated in the OA-prone Hartley compared with Strain 13 animals. Also, at 12 months of age, strain-related differences were apparent for 11 of the 16 cytokines and chemokines. Using multiple linear regression, serum IL-6 and TNF-alpha concentrations were each strongly associated with strain, weight, and their interaction (r(2) = 0.80, P = 0.0002 for IL-6; r(2) = 0.55, P = 0.02 for TNF-alpha).Conclusions: Biomarkers derived from synovial fluid are reflective of histological severity in the spontaneous model of OA in the guinea pig. The synovial fluid biomarker profiles indicated accelerated cartilage matrix turnover in the Hartley strain as early as 2 months of age, prior to evidence of histological damage. The Hartley strain also exemplified an imbalance in type II collagen metabolism and a serum cytokine/chemokine profile indicative of a pro-inflammatory state. These findings elucidate additional disease-related features in the guinea pig that have relevance to OA in humans. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.